- Email: [email protected]
Acute pancreatitis after transcatheter arterial chemoembolization for liver metastases of carcinoid tumors
Clinics and Research in Hepatology and Gastroenterology (2011) 35, 583—585
CASE REPORT
Acute pancreatitis after transcatheter arterial chemoembolization for liver metastases of carcinoid tumors V. Chey a, X. Chopin-laly a, C. Micol c, V. Lepiliez b, J. Forestier a,b, C. Lombard-bohas a, T. Walter a,∗,b a
Service d’oncologie médicale, hôpital Edouard-Herriot, hospices civils de Lyon, 5, place d’Arsonval, 69437 Lyon cedex 03, France Service d’hépato-gastro-entérologie, hôpital Edouard-Herriot, hospices civils de Lyon, 5, place d’Arsonval, 69437 Lyon cedex 03, France c Service de radiologie, hôpital Edouard-Herriot, hospices civils de Lyon, 5, place d’Arsonval, 69437 Lyon cedex 03, France b
Available online 11 February 2011
Summary Acute pancreatitis is a rare side effect of non-selective transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma with an incidence ranging from 2% (clinical pancreatitis) to 40% (biological pancreatitis). This complication, due to embolization of extrahepatic arterial collaterals, has never been reported for treatment of well-differentiated endocrine carcinoma. We report here a case of acute clinical pancreatitis developing within 24 hours after a first selective TACE into the proper hepatic artery, with two peaks of hyperlypasemia, and intend to discuss its mechanism. Since it may clinically mimic a postembolization syndrome, dosage of serum pancreatic enzymes should be performed systematically in case of abdominal pain following TACE. © 2011 Elsevier Masson SAS. All rights reserved.
Transcatheter arterial chemoembolization (TACE) is used to treat liver metastases of well-differentiated endocrine carcinoma (WDEC) especially in case of carcinoid syndrome, which provides a symptomatic response (60—95% of the patients), biological response (50—90%), morphological response (33—80%), and an overall survival of 50—65% at 5 years [1]. Acute pancreatitis (AP) is an uncommon complication of the TACE for hepatocellular carcinoma (2—4% of
∗ Corresponding author. Tel.: +33 4 72 11 00 94; fax: +33 4 72 11 91 53. E-mail address: [email protected] (T. Walter).
clinical presentations). It often occurs 24 hours after TACE [2,3]. We report here the first case of AP after selective TACE for the treatment of liver metastases of pulmonary WDEC. This AP occurred twice in 10 days, prompting discussion about its etiology and treatment. A 60-year-old-man, with no significant medical history, no alcohol consumption, was hospitalized for TACE of liver metastases from a pulmonary WDEC because the carcinoid syndrome was not controlled by somatostatin analogs. The patient had no other clinical symptoms except the carcinoid syndrome. Biological tests of pancreas and liver function were normal. Abdominal computed tomography (CT) showed numerous hypervascular liver metastases, especially in the
2210-7401/$ – see front matter © 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.clinre.2010.12.006
584
V. Chey et al.
Figure 1 Arteriography before (A) and after (B) chemoembolization. The extremity of the intra-arterial catheter is in its own hepatic artery; no extrahepatic collateral artery was visible.
left liver, without portal thrombosis and gallbladder stones. TACE was performed on 10 February 2010 with selective catheterization of the left hepatic artery and injection until cessation of blood flow of 2 mL vial of 500—700 m DC Bead (Biocompatibles, UK). We added 150 mg of diluted doxorubicin into the DC Bead vial (Fig. 1). Twenty-four hours after TACE, the patient presented with abdominal pain after meals, with no fever. The liver-enzyme levels were two times the upper limit of normal range, there was no cholestasis, and serum amylase and lipase levels were 376 U/L and 545 U/L respectively (normal < 60 U/L). AP was suspected and an oral diet was commenced for 3 days until the lipasemia normalised. The evolution of the lipasemia is shown in Fig. 2. CT, performed on 19 February as the lipasemia was again elevated at 327 U/L, showed patchy necrosis in the pancreatic head and isthmus. The Balthazar score of AP was grade D. As a result, oral intake was stopped and an enteral nutrition was started. A second peak of hyperlipasemia (1092 U/L) occurred on 22 February and CT showed an increase of necrosis in the head and the isthmus. Therefore, the enteral nutrition was stopped and was substituted by total parenteral nutrition. The evolution was favorable
Figure 2
with a new normalization of the lipasemia. One month later, there was a third peak of hyperlipasemia which related to a pseudocyst in the head of the pancreas connecting with the main pancreatic duct. An endoscopic retrograde cholangiopancreatography confirmed a tear in the main pancreatic duct and a pancreatic stent was inserted. Finally, on the 68th day after the TACE, the patient had normal physical examination findings and normal laboratory results. Abdominal CT showed decreased pancreatic lesions and the patient was discharged from the hospital. Three months after the procedure, the patient exhibited a decrease of at least 50% in stool and flush frequency; CT scan showed a partial morphologic response, according to Response Evaluation Criteria In Solid Tumors. TACE by selective arterial catheterism is a common treatment for liver metastases of WDEC, particularly in the case of non-controllable carcinoid syndrome [1]. Conventional TACE is usually performed by injecting an emulsion of a drug with iodized oil then embolic agents. However, there is a big heterogeneousness of the protocols of TACE. Moreover, the availability of new embolic products that can be loaded with cytotoxic drugs seems to combine effec-
Evolution of the lipasemia after chemoembolization.
Acute pancreatitis after transcatheter arterial chemoembolization for liver metastases of carcinoid tumors
585
tive embolization and a favourable pharmacokinetic profile. Then de Baere et al. reported in 20 patients that TACE with doxorubicine-eluting beads were well tolerated and appeared effective [4]. However, no comparative studies exist to prove advantages in terms of response and tolerance of this new technique overtreatment with conventional TACE. Even more, although TACE has been used for 20 years, no current evidence exists that conventional TACE is superior to hepatic arterial embolization for the treatments of liver metastases of WDEC. The main complication of TACE, the ‘‘postembolization syndrome’’, is benign with abdominal pains (26 to 55%), vomiting (17 to 50%), fever (33 to 55%) and liver cytolysis. Among the other rare complications, most of them are related to an arterial ischemia, which explain acute cholecystitis (1 to 8% of all cases), duodenal ulcerated complications (hemorrhage or perforation in 1 to 10% of all cases) and AP. This ischemia may be due:
creatic enzymes should be performed systematically in case of abdominal pain following TACE. Cases of AP after TACE are usually benign, occurring within 24 hours, with favorable spontaneous evolution, but some forms with pancreatic necrosis exist. Our observation is unique because the AP occurred twice (two peaks of hyperlipasemia with a gap of 10 days). This can be explained by the natural history of the AP but it could also describe two mechanisms in relation with reflux to the pancreatic artery of the different particles used for TACE [5]: (a) effect of chemotherapy into the DC Beads vial explaining the AP several days later and (b) ischemia due to the embospheres explaining the AP 24 hours after the TACE. At last, a relatively new protocol of TACE was used here, with doxorubicin-eluting beads, which is known to increase necrosis. Therefore, in case of reflux during the procedure or embolization of accessory hepatic artery, more serious ischemic complications may occur.
• by an erratic embolization of accessory hepatic artery; • by reflux of embolic and chemotherapeutic agents into the pancreatic arteries.
Conflict of interest statement
In our case, TACE was the first possible etiology of AP because: • the patient had never had AP before TACE; • the chronology was compatible; • there were no other causes of AP such as a alcoholic consumption, gallbladder stones (and absence of important cytolysis or cholestasis during AP), pancreatic tumor, autoimmune pancreatitis, hypercalcemia, or hypertriglyceridemia; • ischemia is a reported cause of AP by choc hypovolemia or vascular interventions [5,6]; • the vascular opacification had showed no anatomic arterial variation and no vascular spasm itself during the arteriography, but a reflux during the procedure was retrospectively detected on imaging angiography despite selective TACE in the proper hepatic artery. Biological pancreatitis, with an elevation of serum lipase levels alone, was frequent to 40% of the cases in a series of 20 patients [5]. It is necessary to diagnose AP early when abdominal pains present after TACE. Since AP may mimic a postembolization syndrome, dosage of serum pan-
None.
References [1] Vogl TJ, Naguib NN, Zangos S, Eichler K, Hedayati A, Nour-Eldin NE. Liver metastases of neuroendocrine carcinomas: interventional treatment via transarterial embolization, chemoembolization and thermal ablation. Eur J Radiol 2009;72:517—28. [2] López-Benítez R, Radeleff BA, Barragán-Campos HM, Noeldge G, Grenacher L, Richter GM, et al. Acute pancreatitis after embolization of liver tumors: frequency and associated risk factors. Pancreatology 2007;7:53—62. [3] Ozc ¸inar B, Güven K, Poyanli A, Ozden I. Necrotizing pancreatitis after transcatheter arterial chemoembolization for hepatocellular carcinoma. Diagn Interv Radiol 2009;15:36—8. [4] de Baere T, Deschamps F, Teriitheau C, Rao P, Conengrapht K, Sclumberger M, et al. Transarterial chemoembolization of liver metastases from well differentiated gastroenteropancreatic endocrine tumors with doxorubicin-eluting beads: preliminary results. J Vasc Interv Radiol 2008;19:855—61. [5] Khan KN, Nakata K, Shima M, Kusumoto Y, Nobuko I, Koji T, et al. Pancreatic tissue damage by transcatheter arterial embolization for hepatoma. Dig Dis Sci 1993;38:65—70. [6] Roullet MH, Denys A, Sauvanet A, Farges O, Vilgrain V, Belghiti V. Pancréatite aiguë clinique après chimio-embolisation sélective d’un carcinome hépatocellulaire. Ann Chir 2002;127:779—82.
CASE REPORT
Acute pancreatitis after transcatheter arterial chemoembolization for liver metastases of carcinoid tumors V. Chey a, X. Chopin-laly a, C. Micol c, V. Lepiliez b, J. Forestier a,b, C. Lombard-bohas a, T. Walter a,∗,b a
Service d’oncologie médicale, hôpital Edouard-Herriot, hospices civils de Lyon, 5, place d’Arsonval, 69437 Lyon cedex 03, France Service d’hépato-gastro-entérologie, hôpital Edouard-Herriot, hospices civils de Lyon, 5, place d’Arsonval, 69437 Lyon cedex 03, France c Service de radiologie, hôpital Edouard-Herriot, hospices civils de Lyon, 5, place d’Arsonval, 69437 Lyon cedex 03, France b
Available online 11 February 2011
Summary Acute pancreatitis is a rare side effect of non-selective transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma with an incidence ranging from 2% (clinical pancreatitis) to 40% (biological pancreatitis). This complication, due to embolization of extrahepatic arterial collaterals, has never been reported for treatment of well-differentiated endocrine carcinoma. We report here a case of acute clinical pancreatitis developing within 24 hours after a first selective TACE into the proper hepatic artery, with two peaks of hyperlypasemia, and intend to discuss its mechanism. Since it may clinically mimic a postembolization syndrome, dosage of serum pancreatic enzymes should be performed systematically in case of abdominal pain following TACE. © 2011 Elsevier Masson SAS. All rights reserved.
Transcatheter arterial chemoembolization (TACE) is used to treat liver metastases of well-differentiated endocrine carcinoma (WDEC) especially in case of carcinoid syndrome, which provides a symptomatic response (60—95% of the patients), biological response (50—90%), morphological response (33—80%), and an overall survival of 50—65% at 5 years [1]. Acute pancreatitis (AP) is an uncommon complication of the TACE for hepatocellular carcinoma (2—4% of
∗ Corresponding author. Tel.: +33 4 72 11 00 94; fax: +33 4 72 11 91 53. E-mail address: [email protected] (T. Walter).
clinical presentations). It often occurs 24 hours after TACE [2,3]. We report here the first case of AP after selective TACE for the treatment of liver metastases of pulmonary WDEC. This AP occurred twice in 10 days, prompting discussion about its etiology and treatment. A 60-year-old-man, with no significant medical history, no alcohol consumption, was hospitalized for TACE of liver metastases from a pulmonary WDEC because the carcinoid syndrome was not controlled by somatostatin analogs. The patient had no other clinical symptoms except the carcinoid syndrome. Biological tests of pancreas and liver function were normal. Abdominal computed tomography (CT) showed numerous hypervascular liver metastases, especially in the
2210-7401/$ – see front matter © 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.clinre.2010.12.006
584
V. Chey et al.
Figure 1 Arteriography before (A) and after (B) chemoembolization. The extremity of the intra-arterial catheter is in its own hepatic artery; no extrahepatic collateral artery was visible.
left liver, without portal thrombosis and gallbladder stones. TACE was performed on 10 February 2010 with selective catheterization of the left hepatic artery and injection until cessation of blood flow of 2 mL vial of 500—700 m DC Bead (Biocompatibles, UK). We added 150 mg of diluted doxorubicin into the DC Bead vial (Fig. 1). Twenty-four hours after TACE, the patient presented with abdominal pain after meals, with no fever. The liver-enzyme levels were two times the upper limit of normal range, there was no cholestasis, and serum amylase and lipase levels were 376 U/L and 545 U/L respectively (normal < 60 U/L). AP was suspected and an oral diet was commenced for 3 days until the lipasemia normalised. The evolution of the lipasemia is shown in Fig. 2. CT, performed on 19 February as the lipasemia was again elevated at 327 U/L, showed patchy necrosis in the pancreatic head and isthmus. The Balthazar score of AP was grade D. As a result, oral intake was stopped and an enteral nutrition was started. A second peak of hyperlipasemia (1092 U/L) occurred on 22 February and CT showed an increase of necrosis in the head and the isthmus. Therefore, the enteral nutrition was stopped and was substituted by total parenteral nutrition. The evolution was favorable
Figure 2
with a new normalization of the lipasemia. One month later, there was a third peak of hyperlipasemia which related to a pseudocyst in the head of the pancreas connecting with the main pancreatic duct. An endoscopic retrograde cholangiopancreatography confirmed a tear in the main pancreatic duct and a pancreatic stent was inserted. Finally, on the 68th day after the TACE, the patient had normal physical examination findings and normal laboratory results. Abdominal CT showed decreased pancreatic lesions and the patient was discharged from the hospital. Three months after the procedure, the patient exhibited a decrease of at least 50% in stool and flush frequency; CT scan showed a partial morphologic response, according to Response Evaluation Criteria In Solid Tumors. TACE by selective arterial catheterism is a common treatment for liver metastases of WDEC, particularly in the case of non-controllable carcinoid syndrome [1]. Conventional TACE is usually performed by injecting an emulsion of a drug with iodized oil then embolic agents. However, there is a big heterogeneousness of the protocols of TACE. Moreover, the availability of new embolic products that can be loaded with cytotoxic drugs seems to combine effec-
Evolution of the lipasemia after chemoembolization.
Acute pancreatitis after transcatheter arterial chemoembolization for liver metastases of carcinoid tumors
585
tive embolization and a favourable pharmacokinetic profile. Then de Baere et al. reported in 20 patients that TACE with doxorubicine-eluting beads were well tolerated and appeared effective [4]. However, no comparative studies exist to prove advantages in terms of response and tolerance of this new technique overtreatment with conventional TACE. Even more, although TACE has been used for 20 years, no current evidence exists that conventional TACE is superior to hepatic arterial embolization for the treatments of liver metastases of WDEC. The main complication of TACE, the ‘‘postembolization syndrome’’, is benign with abdominal pains (26 to 55%), vomiting (17 to 50%), fever (33 to 55%) and liver cytolysis. Among the other rare complications, most of them are related to an arterial ischemia, which explain acute cholecystitis (1 to 8% of all cases), duodenal ulcerated complications (hemorrhage or perforation in 1 to 10% of all cases) and AP. This ischemia may be due:
creatic enzymes should be performed systematically in case of abdominal pain following TACE. Cases of AP after TACE are usually benign, occurring within 24 hours, with favorable spontaneous evolution, but some forms with pancreatic necrosis exist. Our observation is unique because the AP occurred twice (two peaks of hyperlipasemia with a gap of 10 days). This can be explained by the natural history of the AP but it could also describe two mechanisms in relation with reflux to the pancreatic artery of the different particles used for TACE [5]: (a) effect of chemotherapy into the DC Beads vial explaining the AP several days later and (b) ischemia due to the embospheres explaining the AP 24 hours after the TACE. At last, a relatively new protocol of TACE was used here, with doxorubicin-eluting beads, which is known to increase necrosis. Therefore, in case of reflux during the procedure or embolization of accessory hepatic artery, more serious ischemic complications may occur.
• by an erratic embolization of accessory hepatic artery; • by reflux of embolic and chemotherapeutic agents into the pancreatic arteries.
Conflict of interest statement
In our case, TACE was the first possible etiology of AP because: • the patient had never had AP before TACE; • the chronology was compatible; • there were no other causes of AP such as a alcoholic consumption, gallbladder stones (and absence of important cytolysis or cholestasis during AP), pancreatic tumor, autoimmune pancreatitis, hypercalcemia, or hypertriglyceridemia; • ischemia is a reported cause of AP by choc hypovolemia or vascular interventions [5,6]; • the vascular opacification had showed no anatomic arterial variation and no vascular spasm itself during the arteriography, but a reflux during the procedure was retrospectively detected on imaging angiography despite selective TACE in the proper hepatic artery. Biological pancreatitis, with an elevation of serum lipase levels alone, was frequent to 40% of the cases in a series of 20 patients [5]. It is necessary to diagnose AP early when abdominal pains present after TACE. Since AP may mimic a postembolization syndrome, dosage of serum pan-
None.
References [1] Vogl TJ, Naguib NN, Zangos S, Eichler K, Hedayati A, Nour-Eldin NE. Liver metastases of neuroendocrine carcinomas: interventional treatment via transarterial embolization, chemoembolization and thermal ablation. Eur J Radiol 2009;72:517—28. [2] López-Benítez R, Radeleff BA, Barragán-Campos HM, Noeldge G, Grenacher L, Richter GM, et al. Acute pancreatitis after embolization of liver tumors: frequency and associated risk factors. Pancreatology 2007;7:53—62. [3] Ozc ¸inar B, Güven K, Poyanli A, Ozden I. Necrotizing pancreatitis after transcatheter arterial chemoembolization for hepatocellular carcinoma. Diagn Interv Radiol 2009;15:36—8. [4] de Baere T, Deschamps F, Teriitheau C, Rao P, Conengrapht K, Sclumberger M, et al. Transarterial chemoembolization of liver metastases from well differentiated gastroenteropancreatic endocrine tumors with doxorubicin-eluting beads: preliminary results. J Vasc Interv Radiol 2008;19:855—61. [5] Khan KN, Nakata K, Shima M, Kusumoto Y, Nobuko I, Koji T, et al. Pancreatic tissue damage by transcatheter arterial embolization for hepatoma. Dig Dis Sci 1993;38:65—70. [6] Roullet MH, Denys A, Sauvanet A, Farges O, Vilgrain V, Belghiti V. Pancréatite aiguë clinique après chimio-embolisation sélective d’un carcinome hépatocellulaire. Ann Chir 2002;127:779—82.